The present invention is concerned with an Equine herpesvirus-4 mutant (EHV-4), a recombinant DNA molecule comprising EHV-4 DNA, host cell containing said recombinant DNA molecule, process for the preparation of said EHV-4 mutant, cell culture infected with the EHV-4 mutant, a vaccine derived from the EHV-4 mutant as well as a process for the preparation of such a vaccine.
Equine herpesvirus-4 (EHV-4) is, like the related Equine herpesvirus-1, an alphaherpesvirus responsible for significant economic losses within the equine industry. EHV-4 is primarily associated with respiratory disease though EHV-4 induced abortions are occasionally reported.
The genome of EHV-4 has been characterized as a double-stranded linear DNA molecule consisting of two covalently linked segments (L, 109 kbp; S, 35 kbp) the latter being flanked by inverted repeats.
Control by vaccination of EHV-4 infection has been a long-sought goal.
Current vaccines comprise chemically inactivated virus vaccines and modified live-virus vaccines. However, inactivated vaccines generally induce only a low level of immunity, requiring additional immunizations, disadvantageously require adjuvants and are expensive to produce. Further, some infectious virus particles may survive the inactivation process and causes disease after administration to the animal.
In general, attenuated live virus vaccines are preferred because they evoke a more long-lasting immune response (often both humoral and cellular) and are easier to produce.
Up to now only live attenuated, EHV-4 vaccines are available which are based on live EHV-4 viruses attenuated by serial passages of virulent strains in tissue culture. However, because of this treatment uncontrolled mutations are introduced into the viral genome, resulting in a population of virus particles heterogeneous in their virulence and immunizing properties. In addition it is well known that such traditional attenuated live virus vaccines can revert to virulence resulting in disease of the inoculated animals and the possible spread of the pathogen to other animals. Furthermore, with the existing live attenuated EHV-4 vaccines a positive serological test is obtained for EHV-4 infection. Thus, with the existing EHV-4 vaccines, it is not possible to determine by a (serological) test, e.g. an Elisa, whether a specific animal is a (latent) carrier of the virulent virus or is vaccinated.